Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Electrochemical oxidative aminocarbonylation of terminal alkynes

Abstract

Palladium-catalysed oxidative carbonylation using oxygen as the oxidant is an economical approach; however, the gas mixture of CO and air has an explosive limit of 12.5–74.0% that could hamper extensive application of this process. Herein we report an electrochemical aminocarbonylation of alkynes under atmospheric pressure in an undivided cell without an external oxidant. The transformation has a broad substrate scope (83 examples) that involves primary amines and ammonium salts. Furthermore, mechanistic studies through cyclic voltammetry, in situ infrared and quick-scanning X-ray absorption fine structure spectroscopy reveal the reasons for this protocol proceeding smoothly under electrochemical conditions.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Electrochemical oxidative aminocarbonylation of terminal alkynes.
Fig. 2: Cyclic voltammetry studies.
Fig. 3: In situ infrared studies.
Fig. 4: XAFS studies.
Fig. 5: Mechanistic investigation.
Fig. 6: The substrate scope for the aminocarbonylation of primary and secondary amines.
Fig. 7: The substrate scope for the aminocarbonylation of ammonium salts.

Data availability

All data including experimental procedures and compound characterization are available within the paper and its Supplementary Information. All other data are available from the authors on reasonable request.

References

  1. 1.

    Barnard, C. F. J. Palladium-catalyzed carbonylation—a reaction come of age. Organometallics 27, 5402–5422 (2008).

    CAS  Google Scholar 

  2. 2.

    Brennführer, A., Neumann, H. & Beller, M. Palladium-catalyzed carbonylation reactions of aryl halides and related compounds. Angew. Chem. Int. Ed. 48, 4114–4133 (2009).

    Google Scholar 

  3. 3.

    Shen, C. & Wu, X.-F. Palladium-catalyzed carbonylative multicomponent reactions. Chem. Eur. J. 23, 2973–2987 (2017).

    CAS  PubMed  Google Scholar 

  4. 4.

    Sumino, S., Fusano, A., Fukuyama, T. & Ryu, I. Carbonylation reactions of alkyl iodides through the interplay of carbon radicals and Pd catalysts. Acc. Chem. Res. 47, 1563–1574 (2014).

    CAS  PubMed  Google Scholar 

  5. 5.

    Kiss, G. Palladium-catalyzed reppe carbonylation. Chem. Rev. 101, 3435–3456 (2001).

    CAS  PubMed  Google Scholar 

  6. 6.

    Li, S., Chen, G., Feng, C.-G., Gong, W. & Yu, J.-Q. Ligand-enabled γ-C–H olefination and carbonylation: construction of β-quaternary carbon centers. J. Am. Chem. Soc. 136, 5267–5270 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Liu, C. et al. Oxidative coupling between two hydrocarbons: an update of recent C–H functionalizations. Chem. Rev. 115, 12138–12204 (2015).

    CAS  PubMed  Google Scholar 

  8. 8.

    Liu, Q., Zhang, H. & Lei, A. Oxidative carbonylation reactions: organometallic compounds (R–M) or hydrocarbons (R–H) as nucleophiles. Angew. Chem. Int. Ed. 50, 10788–10799 (2011).

    CAS  Google Scholar 

  9. 9.

    Willcox, D. et al. A general catalytic β-C–H carbonylation of aliphatic amines to β-lactams. Science 354, 851–857 (2016).

    CAS  PubMed  Google Scholar 

  10. 10.

    Wu, X.-F., Neumann, H. & Beller, M. Palladium-catalyzed oxidative carbonylation reactions. ChemSusChem 6, 229–241 (2013).

    CAS  PubMed  Google Scholar 

  11. 11.

    Carl, Y. & William, B. Matheson Gas Data Book (McGraw-Hill Professional, 2001).

  12. 12.

    Francke, R. & Little, R. D. Redox catalysis in organic electrosynthesis: basic principles and recent developments. Chem. Soc. Rev. 43, 2492–2521 (2014).

    CAS  PubMed  Google Scholar 

  13. 13.

    Frontana-Uribe, B. A., Little, R. D., Ibanez, J. G., Palma, A. & Vasquez-Medrano, R. Organic electrosynthesis: a promising green methodology in organic chemistry. Green. Chem. 12, 2099–2119 (2010).

    CAS  Google Scholar 

  14. 14.

    Huang, X., Zhang, Q., Lin, J., Harms, K. & Meggers, E. Electricity-driven asymmetric Lewis acid catalysis. Nat. Catal. 2, 34–40 (2019).

    CAS  Google Scholar 

  15. 15.

    Jiang, Y., Xu, K. & Zeng, C. Use of electrochemistry in the synthesis of heterocyclic structures. Chem. Rev. 118, 4485–4540 (2017).

    PubMed  Google Scholar 

  16. 16.

    Jutand, A. Contribution of electrochemistry to organometallic catalysis. Chem. Rev. 108, 2300–2347 (2008).

    CAS  PubMed  Google Scholar 

  17. 17.

    Sperry, J. B. & Wright, D. L. The application of cathodic reductions and anodic oxidations in the synthesis of complex molecules. Chem. Soc. Rev. 35, 605–621 (2006).

    CAS  PubMed  Google Scholar 

  18. 18.

    Tang, S., Liu, Y. & Lei, A. Electrochemical oxidative cross-coupling with hydrogen evolution: a green and sustainable way for bond formation. Chem 4, 27–45 (2018).

    CAS  Google Scholar 

  19. 19.

    Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemical methods since 2000: on the verge of a renaissance. Chem. Rev. 117, 13230–13319 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Yoshida, J.-i, Kataoka, K., Horcajada, R. & Nagaki, A. Modern strategies in electroorganic synthesis. Chem. Rev. 108, 2265–2299 (2008).

    CAS  PubMed  Google Scholar 

  21. 21.

    Chiarotto, I. & Carelli, I. Palladium-catalyzed electrochemical carbonylation of alkynes under very mild conditions. Synth. Commun. 32, 881–886 (2002).

    CAS  Google Scholar 

  22. 22.

    Ma, C., Fang, P. & Mei, T.-S. Recent advances in C–H functionalization using electrochemical transition metal catalysis. ACS Catal. 8, 7179–7189 (2018).

    CAS  Google Scholar 

  23. 23.

    Moeller, K. D. Using physical organic chemistry to shape the course of electrochemical reactions. Chem. Rev. 118, 4817–4833 (2018).

    CAS  PubMed  Google Scholar 

  24. 24.

    Sauermann, N., Meyer, T. H., Qiu, Y. & Ackermann, L. Electrocatalytic C–H activation. ACS Catal. 8, 7086–7103 (2018).

    CAS  Google Scholar 

  25. 25.

    Xu, F., Li, Y.-J., Huang, C. & Xu, H.-C. Ruthenium-catalyzed electrochemical dehydrogenative alkyne annulation. ACS Catal. 8, 3820–3824 (2018).

    CAS  Google Scholar 

  26. 26.

    Zhang, L. et al. Photoelectrocatalytic arene C–H amination. Nat. Catal. 2, 366–373 (2019).

    CAS  Google Scholar 

  27. 27.

    Wiebe, A. et al. Electrifying organic synthesis. Angew. Chem. Int. Ed. 57, 5594–5619 (2018).

    CAS  Google Scholar 

  28. 28.

    Fu, N., Sauer, G. S., Saha, A., Loo, A. & Lin, S. Metal-catalyzed electrochemical diazidation of alkenes. Science 357, 575–579 (2017).

    CAS  PubMed  Google Scholar 

  29. 29.

    Gabriele, B., Salerno, G., Veltri, L. & Costa, M. Synthesis of 2-ynamides by direct palladium-catalyzed oxidative aminocarbonylation of alk-1-ynes. J. Organomet. Chem. 622, 84–88 (2001).

    CAS  Google Scholar 

  30. 30.

    Gadge, S. T., Khedkar, M. V., Lanke, S. R. & Bhanage, B. M. Oxidative aminocarbonylation of terminal alkynes for the synthesis of alk-2-ynamides by using palladium-on-carbon as efficient, heterogeneous, phosphine-free, and reusable catalyst. Adv. Synth. Catal. 354, 2049–2056 (2012).

    CAS  Google Scholar 

  31. 31.

    Hughes, N. L., Brown, C. L., Irwin, A. A., Cao, Q. & Muldoon, M. J. Palladium(ii)-catalysed aminocarbonylation of terminal alkynes for the synthesis of 2-ynamides: addressing the challenges of solvents and gas mixtures. ChemSusChem 10, 675–680 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Veltri, L. et al. A palladium iodide-catalyzed oxidative aminocarbonylation–heterocyclization approach to functionalized benzimidazoimidazoles. J. Org. Chem. 83, 1680–1685 (2018).

    CAS  PubMed  Google Scholar 

  33. 33.

    Zhang, C., Liu, J. & Xia, C. Palladium–N-heterocyclic carbene (NHC)-catalyzed synthesis of 2-ynamides via oxidative aminocarbonylation of alkynes with amines. Catal. Sci. Technol. 5, 4750–4754 (2015).

    CAS  Google Scholar 

  34. 34.

    Choi, Y.-S. et al. Ionic liquids as benign catalysts for the carbonylation of amines to formamides. Appl. Catal. A Gen. 404, 87–92 (2011).

    CAS  Google Scholar 

  35. 35.

    Gerack, C. J. & McElwee-White, L. Oxidative carbonylation of amines to formamides using NaIO4. Chem. Commun. 48, 11310–11312 (2012).

    CAS  Google Scholar 

  36. 36.

    Li, X. et al. N-Heterocyclic carbene catalyzed direct carbonylation of dimethylamine. Chem. Commun. 47, 7860–7862 (2011).

    CAS  Google Scholar 

  37. 37.

    Preiß, S. et al. Structure and reactivity of a mononuclear gold(ii) complex. Nat. Chem. 9, 1249–1255 (2017).

    PubMed  Google Scholar 

  38. 38.

    Yuan, N. et al. Probing the evolution of palladium species in Pd@MOF catalysts during the heck coupling reaction: an operando X‑ray absorption spectroscopy study. J. Am. Chem. Soc. 140, 8206–8217 (2018).

    CAS  PubMed  Google Scholar 

  39. 39.

    Venderbosch, B. et al. Spectroscopic investigation of the activation of a chromium-pyrrolyl ethene trimerization catalyst. ACS Catal. 9, 1197–1210 (2019).

    CAS  PubMed  Google Scholar 

  40. 40.

    Tran, B. et al. Operando XAFS studies on Rh(CAAC)-catalyzed arene hydrogenation. ACS Catal. 9, 4106–4114 (2019).

    CAS  Google Scholar 

  41. 41.

    Yi, H. et al. Unravelling the hidden link of lithium halides and application in the synthesis of organocuprates. Nat. Commun. 8, 14794 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Bai, R. et al. Cu(ii)/Cu(i)-synergistic cooperation to lead the alkyne C–H activation. J. Am. Chem. Soc. 136, 16760–16763 (2014).

    CAS  PubMed  Google Scholar 

  43. 43.

    Zhang, G. et al. Direct observation of reduction of Cu(ii) to Cu(i) by terminal alkynes. J. Am. Chem. Soc. 136, 924–926 (2014).

    CAS  PubMed  Google Scholar 

  44. 44.

    Izawa, Y., Shimizu, I. & Yamamoto, A. Palladium-catalyzed oxidative carbonylation of 1-alkynes into 2-alkynoates with molecular oxygen as oxidant. B. Chem. Soc. Jpn. 77, 2033–2045 (2004).

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant nos. 21520102003, 21702152), the 973 Program (grant no. 2012CB725302), the CAS Interdisciplinary Innovation Team and the Hubei Province Natural Science Foundation of China (grant no. 2017CFA010). The Program of Introducing Talents of Discipline to Universities of China (111 Program) is also appreciated. X-ray absorption spectroscopy analysis was performed at the National Synchrotron Radiation Research Center (44A in Taiwan Photon Source). We would like to thank O. Muller from Bergische University Wuppertal for providing JAQ Analyzes QEXAFS software for analysing Quick-XAFS data. We would like to thank G. Li from State Utah University and S. Tang from the Weizmann Institute of Science for advising on the manuscript.

Author information

Affiliations

Authors

Contributions

A.L., Y.-H.C. and L.Z. contributed to the conception and design of the experiments. H.L., Jingcheng H., D.Z., Jiayu H., P.P., S.W., R.S., J.P., C.-W.P., J.-L.C., J.-F.L. and H.Z. performed the experiments. L.Z., Y.-H.C. and A.L. co-wrote the manuscript and all authors contributed to data analysis and scientific discussion.

Corresponding authors

Correspondence to Yi-Hung Chen or Aiwen Lei.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Methods, Tables 1–6, Figs. 1–36 and references.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zeng, L., Li, H., Hu, J. et al. Electrochemical oxidative aminocarbonylation of terminal alkynes. Nat Catal 3, 438–445 (2020). https://doi.org/10.1038/s41929-020-0443-z

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing